Stand-by emergency treatment

An individual who experiences a fever 1 week or more after entering an area of malaria risk should consult a physician or qualified malaria laboratory immediately to obtain diagnosis and treatment. Most travellers will be able to obtain medical attention within 24 hours of the onset of fever. For a minority, however, this may be impossible, particularly if they will be staying (1 week or more after entering an endemic area) in a remote location. In such cases, travellers are advised to carry antimalarial drugs for self-administration (“stand-by emergency treatment”). The choice of drugs for stand-by emergency treatments in relation to the drugs used for prophylaxis is given in Table 7.1.
 

Stand-by emergency treatment may also be indicated for travellers in some occupational groups, such as aircraft crews, who make frequent short stops in endemic areas over a prolonged period of time. Such travellers may eventually choose to reserve chemoprophylaxis for high-risk areas only. However, they should continue to take rigorous measures for protection against mosquito bites and be prepared for an attack of malaria: they should always carry a course of antimalarial drugs for stand-by emergency treatment, seek immediate medical care in case of fever, and take stand-by emergency treatment if prompt medical help is not available.
Stand-by emergency treatment—combined with rigorous protection against mosquito bites—may occasionally be indicated for those who travel for 1 week or more to remote rural areas where there is a very low likelihood of multidrug-resistant malaria and the risk of side-effects of prophylaxis outweighs the risk of contracting malaria. This may be the case in certain border areas of countries in south-east Asia where the risk of side-effects may outweigh the risk of becoming infected. However, most travellers to these areas will be able to access competent medical care within 24 hours of the onset of fever.
 

Studies on the use of rapid diagnostic tests (“dipsticks”) have shown that untrained travellers experience major problems in the performance and interpretation of these tests, with an unacceptably high number of false-negative results. Major technical modifications are required before dipsticks can be recommended for use by travellers.
Travellers provided with stand-by emergency treatment should be given clear and precise written instructions on the recognition of symptoms, when and how to take the treatment, the treatment regimen, possible side-effects, and the possibility of drug failure. They should be made aware that self-treatment is a first-aid measure, and that they should seek medical advice as soon as possible.
 

In general, travellers carrying stand-by emergency treatment should observe the following guidelines:
 

• Consult a physician immediately if fever occurs 1 week or more after entering an area with malaria risk.
   
• If it is impossible to consult a physician and/or establish a diagnosis within 24 hours of the onset of fever, start the stand-by emergency treatment and seek medical care as soon as possible for complete evaluation and to exclude other serious causes of fever.
   
• Complete the stand-by treatment course and resume antimalarial prophylaxis 1 week after the first treatment dose. Mefloquine prophylaxis, however, should be resumed 1 week after the last treatment dose of quinine.
   
• Vomiting of antimalarial drugs is less likely if fever is first lowered with antipyretics. A second full dose should be taken if vomiting occurs within
  30 minutes of taking the drug. If vomiting occurs 30–60 minutes after a dose, an additional half-dose should be taken. Vomiting with diarrhoea may lead to treatment failure because of poor drug absorption.
   

Depending on the area visited and the chemoprophylaxis regimen taken, one of the following stand-by treatment regimens can be recommended.

• Chloroquine

Adults: 1500 mg chloroquine base total, taken as 6 tablets of 100 mg, followed by 6 tablets 24 hours later, and 3 tablets 48 hours after the first dose.
Children: a total dose of 25 mg chloroquine base per kg body weight over 3 days, taken as 10 mg per kg on the first and second day, and 5 mg per kg on the third day.

• Sulfadoxine–pyrimethamine

Adults: single dose of 3 tablets, each containing 500 mg sulfadoxine plus 25 mg pyrimethamine.
Children: single dose of 25 mg sulfadoxine plus 1.25 mg pyrimethamine per kg body weight.

• Mefloquine

Mefloquine is contraindicated during the first 3 months of pregnancy and in infants weighing less than 5 kg.

15 mg base/kg (single dose) or 25 mg base/kg (split dose) depending on the extent of mefloquine resistance in the area concerned.

• Quinine

Adults: 2 tablets of 300 mg quinine, 3 times daily, at 8-hour intervals, for 7 days.
Children: 8 mg quinine base per kg body weight, 3 times daily, for 7 days.

• Quinine plus doxycycline

Adults: quinine as above, plus doxycycline for 7 days: 2 tablets of 100 mg doxycycline salt on the first day, 12 hours apart, and 1 tablet daily for the next 6 days.
Children 8 years and older: quinine as above, plus doxycycline treatment for 7 days based on body weight: 25–35 kg, 1/2 adult dose; 36–50 kg, 3/4 adult dose.
 

Doxycycline is contraindicated during pregnancy and lactation, and in children under 8 years of age.
Note. For specific drug contraindications, see Table 7.3.
 

Artemether/lumefantrine has been registered for stand-by emergency treatment in Switzerland only.
Halofantrine is no longer recommended for stand-by treatment following reports that it can result in ventricular dysrhythmias and prolongation of Q–T intervals in susceptible individuals. These changes may be accentuated if halofantrine is taken with other antimalarial drugs that may reduce myocardial conduction.

Treatment of P. vivax, P. ovale and P. malariae infections

P. vivax and P. ovale can remain quiescent in the liver for many months. Relapses caused by the persistent liver forms may appear months, and rarely up to 1–2 years, after exposure. They are not prevented by current chemoprophylactic regimens. Relapses can be treated with chloroquine (or mefloquine or quinine if resistance is suspected) and further relapses prevented by a course of primaquine, which eliminates any remaining parasite in the liver. In patients with known or suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency, expert medical advice should be sought since primaquine may cause haemolysis in G6PD-deficient patients. Where possible, G6PD deficiency should be excluded before antirelapse therapy with primaquine is given. Blood infection with P. malariae may be present for many years, but it is not life-threatening and is easily cured by a standard treatment course of chloroquine.
 

Special groups

Some groups of travellers, especially young children and pregnant women, are at particular risk of serious consequences if they become infected with malaria.
 

Pregnant women

Malaria in a pregnant woman increases the risk of maternal death, miscarriage, stillbirth and low birth weight with associated risk of neonatal death.
Pregnant women should be advised to avoid travelling to areas where chloroquine-resistant P. falciparum occurs. When travel cannot be avoided, it is very important to take effective preventive measures against malaria, even when travelling to areas with transmission of vivax malaria only.
Pregnant women should be extra diligent in using measures to protect against mosquito bites, but should take care not to exceed the recommended dosage of insect repellents.
 

In the few areas with exclusively P. vivax transmission or where P. falciparum can be expected to be 100% sensitive to chloroquine, prophylaxis with chloroquine alone may be used. In areas with chloroquine-resistant P. falciparum, prophylaxis with chloroquine plus proguanil is recommended during the first three months of pregnancy. Mefloquine prophylaxis may be given during the second and the third trimesters. Other drugs are either dangerous to the fetus or have been insufficiently well investigated to be prescribed for prophylaxis in pregnancy.
Pregnant women should seek medical help immediately if malaria is suspected; if this is not possible, they should take emergency stand-by treatment with quinine. Medical help must be sought as soon as possible after stand-by treatment.
 

Pregnant women with falciparum malaria may rapidly develop any of the clinical symptoms of severe malaria. They are particularly susceptible to hypoglycaemia and pulmonary oedema. They may develop postpartum haemorrhage, and hyperpyrexia leading to fetal distress. Any pregnant woman with severe falciparum malaria should be transferred to intensive care, and managed in close collaboration between infectious disease, internal medicine and obstetric care specialists. Because of the risk of quinine-induced hyperinsulinaemia and hypoglycaemia, artesunate and artemether are the drugs of choice for treatment of severe malaria in the second and third trimester. Data on the use of artemisinin derivatives in the first trimester are still limited.
 

Women who may become pregnant during or after travel

Both mefloquine and doxycycline prophylaxis may be taken, but pregnancy should be avoided during the period of drug intake and for 3 months after mefloquine and 1 week after doxycycline prophylaxis is stopped.
If pregnancy occurs during antimalarial prophylaxis, the woman's doctor should give information about the possible effects of the drugs on the fetus. However, in the case of unplanned pregnancy, malaria chemoprophylaxis is not considered to be an indication for pregnancy termination.
 

Young children

Falciparum malaria in a young child is a medical emergency—it may be rapidly fatal. Early symptoms are atypical and difficult to recognize, but life-threatening complications can occur within hours of the initial symptoms.
Parents should be advised not to take babies or young children to areas with transmission of chloroquine-resistant P. falciparum. If travel cannot be avoided, children must be very carefully protected against mosquito bites and be given appropriate chemoprophylactic drugs. Babies should be kept under insecticide-treated mosquito nets as much as possible between dusk and dawn. The manufacturer's instructions on the use of insect repellents should be followed diligently, and the recommended dosage must not be exceeded.
Breastfed, as well as bottle-fed, babies, should be given chemoprophylaxis since they are not protected by the mother's prophylaxis. Dosage schedules for children should be based on body weight. Chloroquine and proguanil are safe for babies and young children, and mefloquine may be given to infants of more than 5 kg body weight. Doxycycline, however, is contraindicated in children below 8 years of age and atovaquone/proguanil cannot be recommended for prophylaxis in children weighing less than 11 kg because of the lack of data.
All antimalarial drugs should be kept out of the reach of children and stored in childproof containers. Chloroquine is particularly toxic to children in case of overdose.
Medical help should be sought immediately if a child develops a febrile illness. Malaria should always be suspected and laboratory diagnosis is essential. In infants, malaria should be suspected even in non-febrile illness.
The possibility of malaria should be considered whenever a child develops a fever within a year of travelling to or immigrating from an endemic area. Laboratory diagnosis should be requested immediately if malaria is suspected, and treatment with an effective antimalarial drug initiated as soon as possible.
 

Special situations—multidrug-resistant malaria

In border areas between Cambodia, Myanmar and Thailand, P. falciparum infections do not respond to treatment with chloroquine or sulfadoxine–pyrimethamine, and sensitivity to quinine is reduced. Treatment failures in excess of 50% with mefloquine are also being reported. In these situations, doxycycline can be used for chemoprophylaxis together with rigorous personal protection measures. However, the drug is contraindicated in pregnant women and children under the age of 8 years. Since there is no prophylactic regimen that is both effective and safe for these groups in areas of multidrug-resistant malaria, pregnant women and young children should avoid travelling to these malarious areas.
The national authorities in Thailand recommend a combination of mefloquine plus artesunate or artemether as the first-line treatment in areas of highly mefloquine-resistant malaria. When these drugs are not available, infections with P. falciparum acquired on the Thailand/Cambodia and Thailand/Myanmar borders may be treated with a total dose of 25 mg/kg mefloquine, given as 15 mg/kg initially followed by 10 mg/kg 6–8 hours later, or with oral quinine, 10 mg/kg of body weight every 8 hours for 7 days, in combination with either tetracycline or doxycycline. In the Amazon basin of south America, mefloquine resistance has been reported only from Brazil, where clinical failure rates remain below 5%

Table 7.1 Choice of stand-by treatment according to recommended chemoprophylactic regimen

Note 1. The choice of drug to be used for stand-by treatment depends on the prophylaxis taken and on the presence of drug-resistant malaria in the countries to be visited (see Country list). The drug selected for stand-by treatment should be one to which no resistance has been reported in the countries concerned.

Note 2. No stand-by treatment can be recommended for travellers taking atovaquone/proguanil prophylaxis because of the lack of data and the possibility of drug interactions.

* In these situations, mefloquine prophylaxis should only be resumed 7 days after the last self-treatment dose of quinine.

Further reading

Management of severe malaria: a practical handbook, 2nd ed. Geneva, WHO, 2000.

WHO Expert Committee on Malaria. Twentieth report. WHO, Geneva, 2000 (WHO Technical Report Series, No. 892).

The use of antimalarial drugs (2001)